Gaithersburg, MD -- May 20, 2010 – Wellstat Therapeutics
announced today that the company’s investigational drug
uridine triacetate has further demonstrated its life-saving
potential in treating patients overexposed to the widely used
cancer chemotherapy 5-fluorouracil (5-FU), according to clinical
data to be presented June 7 at the annual meeting of the American
Society of Clinical Oncology (ASCO) in Chicago.1

The National Institutes of Health estimate that 275,000 patients in
the United States undergo 5-FU therapy annually, and 1,300 die from
5-FU overexposure resulting from accidental overdoses or poor drug
clearance.2 While no antidote for 5-FU overexposure has been
approved by regulatory authorities, uridine triacetate (formerly
known as vistonuridine) has been made available to physicians for
emergency use. 3

Wellstat’s poster presentation at ASCO will report on 37
cases of 5-FU overexposure treated with uridine triacetate. In all
of these cases, the patients recovered from the overexposure, even
though a fatal outcome for at least 27 of them would have been
predicted by the dose and rate of 5-FU administration. In one
extreme case, the patient survived after receiving a 5-FU dose 10
times higher than intended (10,000 mg in three hours instead of
1,000 mg in one hour). In all cases, the emergency treatment
commenced as rapidly as possible after 5-FU overexposure (within 8
to 96 hours), depending on the timing of the request to Wellstat
and the location of the treatment site. Among the patients
receiving uridine triacetate, a few experienced mild nausea and
three of these patients had one episode of vomiting each that may
have been associated with uridine triacetate.

In contrast to these observations, the presentation reports data
from a review of cases in which patients did not receive uridine
triacetate but had received 5-FU overdoses of a similar magnitude
to those in the uridine-triacetate-treated group.4 In this
comparator group, 32 of the 36 patients died. The cases were
reported by the Institute for Safe Medication Practices Canada, the
FDA MAUDE database, and other sources.5

“Since our first report on uridine triacetate at ASCO in
2009, the number of patients treated with this investigational
antidote has more than doubled,” said Michael Bamat, Vice
President, Research and Development, Wellstat. “At ASCO in
2010 we can report on this broader experience, which provides
additional evidence in support of the life-saving potential of
uridine triacetate in treating 5-FU overexposure.”

Wellstat plans to seek regulatory approval of uridine triacetate in
the US, Europe, and other regions. Uridine triacetate has been
granted orphan-drug status by the FDA and the European
Commission.

Accidental overdose versus drug clearance

All of the emergency-use cases to be reported at ASCO resulted
from accidental overdoses of 5-FU, usually due to misprogrammed or
malfunctioning infusion pumps used to administer the drug. But
another common cause of overexposure is thought to be poor drug
clearance: a genetic variation in certain patients results in
deficient levels of an enzyme essential for 5-FU metabolism,
dihydropyrimidine dehydrogenase (DPD). Patients deficient in DPD
may experience severe 5-FU toxicity even when 5-FU is administered
in standard doses. It is estimated that people with complete or
partial DPD deficiency make up 0.1% and 3% of the population,
respectively.

In an additional abstract published at ASCO, Wellstat will report
data from a preclinical study examining the role of uridine
triacetate in reversing 5-FU toxicity due to DPD deficiency.6
Results of this study showed that a standard anti-cancer dose of
5-FU was lethal in mice pre-treated with a DPD inhibitor, then
administered 5-FU, and then treated with placebo only. But when, in
similarly pre-treated mice, 5-FU administration was followed by
uridine triacetate, all mice given uridine triacetate within 24
hours survived. After 24 hours, survival continued to correlate
with time of uridine-triacetate administration, survival rates
being higher among mice given uridine triacetate in earlier time
periods. Uridine triacetate thus may be beneficial in DPD-deficient
patients if they are identified and treated soon enough after they
receive 5-FU.

“Preclinical investigation enables us to examine questions
outside the practical and ethical constraints of the clinical
emergencies for which uridine triacetate has been provided,”
said Reid von Borstel, Vice President, Discovery Research,
Wellstat. “And the preclinical evidence supports what we
would assume—that uridine triacetate could be beneficial in
treating cases of DPD deficiency as well as accidental overdose,
and that the sooner treatment begins, the better.”

5-FU

In use as a cancer drug for decades, 5-FU is a mainstay of
various treatment regimens for solid tumors including those of the
colon, stomach, esophagus, breast, and head and neck. The drug is
most commonly administered by infusion pump at or near what is
considered the maximum tolerated dose. Yet many patients do not
receive optimally effective treatment with 5-FU because of concerns
about dose-limiting toxicity and individual variation in 5-FU
metabolism.7

The incidence of 5-FU overexposure is low though difficult to
quantify. Overexposure may result despite careful selection of
patients and adjustment of dose, both because the effective dose
must often be close to a toxic dose and because patients vary in
their capacity to break down 5-FU and eliminate it from the
body.

About uridine triacetate

Uridine triacetate, formerly known as vistonuridine, is an
orally active prodrug of uridine, meaning that uridine triacetate
is converted to uridine in the body. Once uridine triacetate is
converted to uridine, it reduces the incorporation of 5-FU
metabolites into the genetic material of non-cancerous cells.
Because of the poor bioavailability of oral uridine, however, and
because of complications associated with intravenously administered
uridine, uridine itself is not a clinically viable treatment for
5-FU overexposure. Uridine triacetate delivers about eight-fold
more uridine into the bloodstream than does oral administration of
uridine.

Wellstat is also investigating the potential use of uridine
triacetate when given after 5-FU administration to cancer patients
to achieve higher, more effective doses of 5-FU while preserving an
acceptable margin of safety.

Uridine triacetate does not have marketing approval for any
indication.

About Wellstat Therapeutics Corporation

Wellstat Therapeutics Corporation, a privately held
biopharmaceutical company in Gaithersburg, Maryland, is dedicated
to the discovery, development, and commercialization of innovative
therapeutics that expand the frontier of modern medicine. The
company focuses on oncology, metabolic disorders including
diabetes, and neurometabolic disorders.

Wellstat Therapeutics is part of the Wellstat group of companies,
which are developing therapeutics, vaccines, and point-of-care
diagnostics.

2Federal Register/Vol. 73, No. 129, July 3, 2008.3The emergency
use of an investigational drug requires an Investigational New Drug
(IND) submission to the Food and Drug Administration. The usual
procedure has been to contact the manufacturer and determine
whether the drug can be made available under an IND.

4Whether or not an antidote for 5-FU overexposure is available,
various types of supportive care may be provided, such as growth
factors to stimulate blood-cell production and antibiotics.